Pazopanib Colon Targeted Liposomal Drug Delivery for Colorectal Cancer: High-pressure Homogenization Process Optimization and in-vivo Evaluation

Abstract:

Background: Pazopanib is second-generation tyrosinekinase inhibitor used in Colorectal cancer (CRC) which is effective orally. Targeted liposomal drug delivery will reduce the unwanted side effects of the drug. The application of High-pressure homogenizers for the preparation of systems like liposomes and lipid dispersions is rising because of its ability of vesicle disruption. Aim: Major objective of present research work was to optimize high pressure homogenization process for formulation of colon targeted liposomal drug delivery system of Pazopanib and its in-vivo evaluation. To study the influence of homogenization Pressure and number of cycles on some parameters, such as vesicle size and polydispersity index (PDI). Materials and Methods: The liposomes were formulated with HSPC (Hydrogenated Phosphotidylcholin from Soybean) m-PEG DSPE-2000 (Phospolipid) and Cholesterol using Ethanol injection method followed by downsizing by EmilsiFlex High pressure Homogenizer. Results and Conclusion: The liposomes were evaluated for entrapment efficiency, in-vitro drug release, osmolality, particle size, size distribution, polydispersity index, FEG-SEM and stability studies. Optimization studies concluded that the optimized formulation with homogenization pressure of 1000, 1500, 2000 psi and number of cycle 9, 6, 6 respectivly gives particle size of 109 nm with PDI 0.998 and desirability 0.975. In-vivo studies in wrister rats in which carcino genesis was done using 1,2- dimethylhydrazine (DMH), indicated that Pazopanib liposomes caused significant tumors growth suppression in terms of tumor volume and weight as compared to control. Histo-pathological evaluation showed that the animals treated with pazopanib liposomes had moderate dysplasia where as untreated animals had severe dysplasia.

Key words: Liposome, Pazopanib, High-pressure homogenizer, Colon targeted, Colorectal.